(548f) Calibration Free Reactive Dissolution Kinetic Modeling with In-Situ FBRM, ATR-IR, and Calorimetry

Modeling efficiently the kinetic of dissolving particulate systems, is a key step in several fields, such as for the controlled released of any active pharmaceutical ingredient. Since a decade the Focused Beam Reflectance Measurement (FBRM) technique became the most common method for the direct in-situ study of particulate systems. The FBRM modeling has been addressed by several authors[1]. A majority of these models aim to recover the Particle Size Distribution (PSD) from the Chord Length Distribution (CLD), i.e., the FBRM raw signal. The matrix problem formulation and its inversion has shown to be ill-posed, and several regularization techniques have been proposed. These techniques are often numerically complex and not suitable to be nested in within a calibration free kinetic analysis framework.

In this contribution, a solvent free reactive dissolution is performed in a custom developed dissolution calorimeter and simultaneously monitored by in-situ ATR-IR, calorimetry and FBRM. The kinetic modeling is based on the population balance framework and combined with a calibration free use of the spectroscopic and calorimetric data. Furthermore, we will discuss two quantitative chord length distribution (CLD) to particle size distribution (PSD) transformation options suitable to be nested within the calibration free dissolution modeling strategy.

We acknowledge financial support by the SNF (grant no 200021-113473).

[1] Kail, N., et al. Chem. Eng. Sci., 2009, 69, 984-1000.

[2] Maeder M. and Neuhold Y.-M., Practical Data Analysis in Chemistry. Elsevier, Amsterdam 2007